chr1-84479400-T-C

Variant names:

• chr1-84479400-T-C
• rs973232032
• NM_025065.7:c.119T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025065.7(RPF1):​c.119T>C​(p.Val40Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RPF1 NM_025065.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.69
• Publications: 0 publications found

Genes affected

RPF1 (HGNC:30350): (ribosome production factor 1 homolog) Enables RNA binding activity. Predicted to be involved in maturation of 5.8S rRNA and maturation of LSU-rRNA. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285361 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036752403).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025065.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPF1	NM_025065.7	MANE Select	c.119T>C	p.Val40Ala	missense	Exon 1 of 9	NP_079341.2	Q9H9Y2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPF1	ENST00000370654.6	TSL:1 MANE Select	c.119T>C	p.Val40Ala	missense	Exon 1 of 9	ENSP00000359688.5	Q9H9Y2
	RPF1	ENST00000923273.1		c.119T>C	p.Val40Ala	missense	Exon 1 of 9	ENSP00000593332.1
	RPF1	ENST00000953136.1		c.119T>C	p.Val40Ala	missense	Exon 1 of 9	ENSP00000623195.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152162 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461790 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727188

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111958

Other (OTH) AF: 0.00 AC: 0 AN: 60392

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152162 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74322

African (AFR) AF: 0.0000483 AC: 2 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.047
DANN	Benign	0.48
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		-1.7
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.011
Sift	Benign	0.42	T
Sift4G	Benign	0.78	T
Polyphen		0.0	B
Vest4		0.062
MutPred		0.14		Gain of relative solvent accessibility (P = 0.0215)
MVP		0.47
MPC		0.16
ClinPred		0.27	T
GERP RS		-9.0
PromoterAI		0.093	Neutral
Varity_R		0.022
gMVP		0.11
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs973232032; hg19: chr1-84945083;